tbuckley/cabot-search huggingface dataset:
Advancing Peripheral Artery Disease Quality of Care and Outcomes Through Patient-Reported Health Status Assessment: A Scientific Statement From the American Heart Association
Authors: Kim G. Smolderen, Olamide Alabi, Tracie C. Collins, Bernard Dennis, Philip P. Goodney, Carlos Mena-Hurtado, John A. Spertus, Carole Decker
Journal: Circulation (2022)

Peripheral artery disease (PAD) is chronic in nature, and individualized chronic disease management is a central focus of care. To accommodate this reality, tools to measure the impact and quality of the PAD care delivered are necessary. Patient-reported outcomes (PROs) and instruments to measure them, that is, PRO measures, have been well studied in the research and clinical trial context, but a shift toward integrating them into clinical practice has yet to take place. A framework to use PRO measures as indicators of the quality of PAD care delivered, that is, PRO performance measures (PRO-PMs), is provided in this scientific statement. Measurement goals to consider by PAD clinical phenotypes are provided, as well as an overview of potential benefits of adopting PRO-PMs in the clinical practice of PAD care, including reducing unwanted variability and promoting health equity. A central discussion with considerations for risk adjustment of PRO-PMs, individualized PAD care, and the need for patient engagement strategies is offered. Furthermore, necessary conditions in terms of required competencies and training to handle PRO-PM data are discussed because the interpretation and handling of these data come with great responsibility and consequences for designing care that adopts a broader framework of risk that goes beyond the inclusion of biomedical variables. To conclude, health system perspectives and an agenda to reach the next steps in the implementation of PRO-PMs in PAD care are offered.
The Unusual Suspect of Carcinoid Tumor: Salivary Gland in Airway Anyone?
Authors: Rastko Rakočević, Curtis Y. Maehara, Shiqian Li, Nariman Saddad, William D. Wallace, Wafaa A. Elatre, Diana H. Yu
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"The Unusual Suspect of Carcinoid Tumor: Salivary Gland in Airway Anyone?." American Journal of Respiratory and Critical Care Medicine, 207(6), pp. 775–776
MonOrail to Cure? Targeting Orai1 to Reverse Pulmonary Arterial Hypertension
Authors: Tatiana V. Kudryashova, Elena A. Goncharova
Journal: Circulation Research (2022)

ulmonary arterial hypertension (PAH) is a progressive and rapidly fatal disease with no cure.In PAH, increased pulmonary vascular resistance and mean pulmonary arterial (PA) pressure (≥20 mmHg at rest) due to vasoconstriction and remodeling of small PAs leads to elevation of right ventricle (RV) afterload and premature death of right heart failure. 1 Over the last decades, development of new therapeutic options significantly improved patients' outcomes.However, available therapies, predominantly vasodilators, do not reverse pulmonary vascular remodeling or stop disease progression, and PAH remains a life-limiting disease with high mortality rates and no curative therapeutic options.
Injury incidence rates in women’s football: a systematic review and meta-analysis of prospective injury surveillance studies
Authors: Dan Horan, Fionn Büttner, Catherine Blake, Martin Hägglund, Seamus Kelly, Eamonn Delahunt
Journal: British Journal of Sports Medicine (2022)

Objective To review the literature to establish overall, match and training injury incidence rates (IIRs) in senior (≥18 years of age) women’s football (amateur club, elite club and international). Design Systematic review and meta-analysis of overall, match and training IIRs in senior women’s football, stratified by injury location, type and severity. Data sources MEDLINE via PubMed; EMBASE via Ovid; CINAHL via EBSCO and Web of Science were searched from earliest record to July 2021. Eligibility criteria for selecting studies (1) football players participating in a senior women’s football league (amateur club or elite club) or a senior women’s international football tournament; (2) the study had to report IIRs or provide sufficient data from which this outcome metric could be calculated through standardised equations; (3) a full-text article published in a peer-reviewed journal before July 2021; (4) a prospective injury surveillance study and (5) case reports on single teams were ineligible. Results 17 articles met the inclusion criteria; amateur club (n=2), elite club (n=10), international (n=5). Overall, match and training ‘time-loss’ IIRs are similar between senior women’s elite club football and international football. ‘Time-loss’ training IIRs in senior women’s elite club football and international football are approximately 6–7 times lower than their equivalent match IIRs. Overall ‘time-loss’ IIRs stratified by injury type in women’s elite club football were 2.70/1000 hours (95% CI 1.12 to 6.50) for muscle and tendon, 2.62/1000 hours (95% CI 1.26 to 5.46) for joint and ligaments, and 0.76/1000 hours (95% CI 0.55 to 1.03) for contusions. Due to the differences in injury definitions, it was not possible to aggregate IIRs for amateur club football. Conclusion Lower limb injuries incurred during matches are a substantial problem in senior women’s football. The prevention of lower limb joint, ligament, muscle and tendon injuries should be a central focus of injury prevention interventions in senior women’s amateur club, elite club and international football. PROSPERO registration number CRD42020162895.
Expression Of Hedgehog Pathway Mediator Gli2 Represents a Clinically Negative Prognostic Marker In Acute Myeloid Leukemia and Its Inhibitor GANT61 Exerts Anti-Leukemic Effects In Vitro
Authors: Jasmin Wellbrock, Julian M Koehler, Katharina Wagner, Emily Latuske, Hauke Stamm, Eik Vettorazzi, Gabi Vohwinkel, Marianne Klokow, Roswitha Kuhling-Thees, Sonja Loges, Michael Amling, Carsten Bokemeyer, Michael Heuser, Juergen Krauter, Walter Fiedler
Journal: Blood (2013)
A virtual chromoendoscopy artificial intelligence system to detect endoscopic and histologic activity/remission and predict clinical outcomes in ulcerative colitis
Authors: Rosanna Cannatelli, Tommaso L. Parigi, Marietta Iacucci, Olga M. Nardone, Gian Eugenio Tontini, Nunzia Labarile, Andrea Buda, Alessandro Rimondi, Alina Bazarova, Raf Bisschops, Rocio del Amor, Pablo Meseguer, Valery Naranjo, Subrata Ghosh, Enrico Grisan
Journal: Endoscopy (2022)

Endoscopic and histological remission (ER, HR) are therapeutic targets in ulcerative colitis (UC). Virtual chromoendoscopy (VCE) improves endoscopic assessment and the prediction of histology; however, interobserver variability limits standardized endoscopic assessment. We aimed to develop an artificial intelligence (AI) tool to distinguish ER/activity, and predict histology and risk of flare from white-light endoscopy (WLE) and VCE videos.1090 endoscopic videos (67 280 frames) from 283 patients were used to develop a convolutional neural network (CNN). UC endoscopic activity was graded by experts using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Paddington International virtual ChromoendoScopy ScOre (PICaSSO). The CNN was trained to distinguish ER/activity on endoscopy videos, and retrained to predict HR/activity, defined according to multiple indices, and predict outcome; CNN and human agreement was measured.The AI system detected ER (UCEIS ≤ 1) in WLE videos with 72 % sensitivity, 87 % specificity, and an area under the receiver operating characteristic curve (AUROC) of 0.85; for detection of ER in VCE videos (PICaSSO ≤ 3), the sensitivity was 79 %, specificity 95 %, and the AUROC 0.94. The prediction of HR was similar between WLE and VCE videos (accuracies ranging from 80 % to 85 %). The model's stratification of risk of flare was similar to that of physician-assessed endoscopy scores.Our system accurately distinguished ER/activity and predicted HR and clinical outcome from colonoscopy videos. This is the first computer model developed to detect inflammation/healing on VCE using the PICaSSO and the first computer tool to provide endoscopic, histologic, and clinical assessment.
Vaccination with Designed Neopeptides Induces Intratumoral, Cross-reactive CD4+ T-cell Responses in Glioblastoma
Authors: Jian Wang, Tobias Weiss, Marian C. Neidert, Nora C. Toussaint, Reza Naghavian, Carla Sellés Moreno, Magdalena Foege, Paula Tomas Ojer, Gioele Medici, Ivan Jelcic, Daniel Schulz, Elisabeth Rushing, Susanne Dettwiler, Barbara Schrörs, Joo Heon Shin, Ron McKay, Catherine J. Wu, Andreas Lutterotti, Mireia Sospedra, Holger Moch, Erich F. Greiner, Bernd Bodenmiller, Luca Regli, Michael Weller, Patrick Roth, Roland Martin
Journal: Clinical Cancer Research (2022)

Abstract Purpose: The low mutational load of some cancers is considered one reason for the difficulty to develop effective tumor vaccines. To overcome this problem, we developed a strategy to design neopeptides through single amino acid mutations to enhance their immunogenicity. Experimental Design: Exome and RNA sequencing as well as in silico HLA-binding predictions to autologous HLA molecules were used to identify candidate neopeptides. Subsequently, in silico HLA-anchor placements were used to deduce putative T-cell receptor (TCR) contacts of peptides. Single amino acids of TCR contacting residues were then mutated by amino acid replacements. Overall, 175 peptides were synthesized and sets of 25 each containing both peptides designed to bind to HLA class I and II molecules applied in the vaccination. Upon development of a tumor recurrence, the tumor-infiltrating lymphocytes (TIL) were characterized in detail both at the bulk and clonal level. Results: The immune response of peripheral blood T cells to vaccine peptides, including natural peptides and designed neopeptides, gradually increased with repetitive vaccination, but remained low. In contrast, at the time of tumor recurrence, CD8+ TILs and CD4+ TILs responded to 45% and 100%, respectively, of the vaccine peptides. Furthermore, TIL-derived CD4+ T-cell clones showed strong responses and tumor cell lysis not only against the designed neopeptide but also against the unmutated natural peptides of the tumor. Conclusions: Turning tumor self-peptides into foreign antigens by introduction of designed mutations is a promising strategy to induce strong intratumoral CD4+ T-cell responses in a cold tumor like glioblastoma.
Defactinib, Pembrolizumab, and Gemcitabine in Patients with Advanced Treatment Refractory Pancreatic Cancer: A Phase I Dose Escalation and Expansion Study
Authors: Andrea Wang-Gillam, Kian-Huat Lim, Robert McWilliams, Rama Suresh, Albert C. Lockhart, Amberly Brown, Marcus Breden, Jad I. Belle, John Herndon, Savannah J. Bogner, Katrina Pedersen, Benjamin Tan, Nicholas Boice, Abhi Acharya, Mina Abdiannia, Feng Gao, Harry H. Yoon, Mojun Zhu, Nikolaos A. Trikalinos, Lee Ratner, Olivia Aranha, William G. Hawkins, Brett H. Herzog, David G. DeNardo
Journal: Clinical Cancer Research (2022)

Targeting focal adhesion kinase (FAK) renders checkpoint immunotherapy effective in pancreatic ductal adenocarcinoma (PDAC) mouse model. Defactinib is a highly potent oral FAK inhibitor that has a tolerable safety profile.We conducted a multicenter, open-label, phase I study with dose escalation and expansion phases. In dose escalation, patients with refractory solid tumors were treated at five escalating dose levels of defactinib and gemcitabine to identify a recommended phase II dose (RP2D). In expansion phase, patients with metastatic PDAC who progressed on frontline treatment (refractory cohort) or had stable disease (SD) after at least 4 months of standard gemcitabine/nab-paclitaxel (maintenance cohort) were treated at RP2D. Pre- and posttreatment tumor biopsies were performed to evaluate tumor immunity.The triple drug combination was well-tolerated, with no dose-limiting toxicities. Among 20 treated patients with refractory PDAC, the disease control rate (DCR) was 80%, with one partial response (PR) and 15 SDs, and the median progression-free survival (PFS) and overall survival (OS) were 3.6 and 7.8 months, respectively. Among 10 evaluable patients in the maintenance cohort, DCR was 70% with one PR and six SDs. Three patients with SD came off study due to treatment- or disease-related complications. The median PFS and OS on study treatment were 5.0 and 8.3 months, respectively.The combination of defactinib, pembrolizumab, and gemcitabine was well-tolerated and safe, had promising preliminary efficacy, and showed biomarker activity in infiltrative T lymphocytes. Efficacy of this strategy may require incorporation of more potent chemotherapy in future studies.
Enhanced Postbronchoscopic Lung Volume Reduction Pneumothorax Detection with Digital Tomosynthesis
Authors: Sameer K. Avasarala, Benjamin Young, Robert C. Gilkeson
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Enhanced Postbronchoscopic Lung Volume Reduction Pneumothorax Detection with Digital Tomosynthesis." American Journal of Respiratory and Critical Care Medicine, 207(6), pp. e47–e48
Comprehensive Molecular Characterization of Gallbladder Carcinoma and Potential Targets for Intervention
Authors: Nicolas A. Giraldo, Esther Drill, Baby A. Satravada, Imane El Dika, A. Rose Brannon, Josephine Dermawan, Abhinita Mohanty, Kerem Ozcan, Debyani Chakravarty, Ryma Benayed, Efsevia Vakiani, Ghassan K. Abou-Alfa, Ritika Kundra, Nikolaus Schultz, Bob T. Li, Michael F. Berger, James J. Harding, Marc Ladanyi, Eileen M. O'Reilly, William Jarnagin, Chad Vanderbilt, Olca Basturk, Maria E. Arcila
Journal: Clinical Cancer Research (2022)

Gallbladder carcinoma (GBC) is an uncommon and aggressive disease, which remains poorly defined at a molecular level. Here, we aimed to characterize the molecular landscape of GBC and identify markers with potential prognostic and therapeutic implications.
Cytokine Storm Syndrome
Authors: Randy Q. Cron, Gaurav Goyal, W. Winn Chatham
Journal: Annual Review of Medicine (2022)

Cytokine storm syndrome (CSS), which is frequently fatal, has garnered increased attention with the ongoing coronavirus pandemic. A variety of hyperinflammatory conditions associated with multiorgan system failure can be lumped under the CSS umbrella, including familial hemophagocytic lymphohistiocytosis (HLH) and secondary HLH associated with infections, hematologic malignancies, and autoimmune and autoinflammatory disorders, in which case CSS is termed macrophage activation syndrome (MAS). Various classification and diagnostic CSS criteria exist and include clinical, laboratory, pathologic, and genetic features. Familial HLH results from cytolytic homozygous genetic defects in the perforin pathway employed by cytotoxic CD8 T lymphocytes and natural killer (NK) cells. Similarly, NK cell dysfunction is often present in secondary HLH and MAS, and heterozygous mutations in familial HLH genes are frequently present. Targeting overly active lymphocytes and macrophages with etoposide and glucocorticoids is the standard for treating HLH; however, more targeted and safer anticytokine (e.g., anti-interleukin-1, -6) approaches are gaining traction as effective alternatives.
A Pragmatic Cluster-Randomized Trial of a Standing Order Entry Intervention for Colony-Stimulating Factor Use Among Patients at Intermediate Risk for Febrile Neutropenia
Authors: Dawn L. Hershman, Aasthaa Bansal, Sean D. Sullivan, William E. Barlow, Kathryn B. Arnold, Kate Watabayashi, Ari Bell-Brown, Nguyet A. Le-Lindqwister, Carrie L. Dul, Ursa A. Brown-Glaberman, Robert J. Behrens, Victor Vogel, Nitya Alluri, Scott D. Ramsey
Journal: Journal of Clinical Oncology (2022)

Primary prophylactic colony-stimulating factors (PP-CSFs) are prescribed to reduce febrile neutropenia (FN) but their benefit for intermediate FN risk regimens is uncertain. Within a pragmatic, randomized trial of a standing order entry (SOE) PP-CSF intervention, we conducted a substudy to evaluate the effectiveness of SOE for patients receiving intermediate-risk regimens.
Anlotinib plus Epirubicin Followed by Anlotinib Maintenance as First-line Treatment for Advanced Soft-tissue Sarcoma: An Open-label, Single-arm, Phase II Trial
Authors: Zhi-ming Wang, Rong-yuan Zhuang, Xi Guo, Chen-lu Zhang, Yang You, Li-sha Chen, Wen-shuai Liu, Yong Zhang, Rong-kui Luo, Ying-yong Hou, Wei-qi Lu, Yu-hong Zhou
Journal: Clinical Cancer Research (2022)

Abstract Purpose: The treatment outcome for locally advanced or metastatic soft-tissue sarcoma (STS) remains unsatisfactory. Anlotinib had demonstrated impressive activity in the subsequent-line treatment of STS. This study investigated the combination of anlotinib and epirubicin followed by anlotinib maintenance as first-line treatment for patients with advanced STS. Patients and Methods: This prospective, open-label, single-arm, phase II trial was conducted in Zhongshan Hospital, Fudan University. Eligible patients were ages 18 years or older and had previously untreated, pathologically confirmed, unresectable locally advanced or metastatic STS. All patients received up to six cycles of anlotinib plus epirubicin followed by anlotinib maintenance until disease progression, unacceptable toxicity, or death. The primary endpoint was the progression-free survival (PFS) rate at 6 months. The study was registered on chictr.org (identifier ChiCTR1900024928). Results: From June 2019 to August 2020, 30 patients were enrolled. By December 2021, the median PFS was 11.5 months [95% confidence interval (CI): 8.6–14.4 months], while the median overall survival was not reached (95% CI: NE–NE). The objective response rate was 13.33% and the disease control rate was 80.0%. The most common adverse events (AE) included anemia (43.3%), nausea/vomiting (40.0%), fatigue (36.7%), leukopenia (30.0%), and proteinuria (10.0%), which were mainly of grade 1 or 2. The most frequent grade 3 or 4 AEs were anemia (10.0%), febrile neutropenia (33.3%), hypothyroidism (3.3%), and leukopenia (3.3%). No treatment-related death occurred. Conclusions: The combination of anlotinib and epirubicin followed by anlotinib maintenance demonstrated promising efficacy with a favorable safety profile.
Low risk of local recurrence after a successful en bloc endoscopic submucosal dissection for noninvasive colorectal lesions with positive horizontal resection margins (R-ESD study)
Authors: Krijn J. C. Haasnoot, Francisco Baldaque-Silva, Arjun Koch, Mariana Figueiredo Ferreira, João Santos-Antunes, Emanuel Dias, Masami Omae, Laurelle van Tilburg, Hao Dang, Arnaud Lemmers, Jurjen J. Boonstra, Leon M. G. Moons
Journal: Endoscopy (2022)

Background During endoscopic submucosal dissection (ESD), the normal mucosa is cut under constant optical control. We studied whether a positive horizontal resection margin after a complete en bloc ESD predicts local recurrence. Methods In this European multicenter cohort study, patients with a complete en bloc colorectal ESD were selected from prospective registries. Cases were defined by a horizontal resection margin that was positive or indeterminate for dysplasia (HM1), whereas controls had a free resection margin (HM0). Low risk lesions with submucosal invasion (T1) and margins free of carcinoma were analyzed separately. The main outcome was local recurrence. Results From 928 consecutive ESDs (2011–2020), 354 patients (40 % female; mean age 67 years, median follow-up 23.6 months), with 308 noninvasive lesions and 46 T1 lesions, were included. The recurrence rate for noninvasive lesions was 1/212 (0.5 %; 95 %CI 0.02 %–2.6 %) for HM0 vs. 2/96 (2.1 %; 95 %CI 0.57 %–7.3 %) for HM1. The recurrence rate for T1 lesions was 1/38 (2.6 %; 95 %CI 0.14 %–13.5 %) for HM0 vs. 2/8 (25 %; 95 %CI 7.2 %–59.1 %) for HM1. Conclusion A positive horizontal resection margin after an en bloc ESD for noninvasive lesions is associated with a marginal nonsignificant increase in the local recurrence rate, equal to an ESD with clear horizontal margins. This could not be confirmed for T1 lesions.
2022 ACC Health Policy Statement on Career Flexibility in Cardiology
Authors: Mary Norine Walsh, James A. Arrighi, Joseph G. Cacchione, Anna Lisa Chamis, Pamela S. Douglas, Claire S. Duvernoy, JoAnne M. Foody, Sharonne N. Hayes, Dipti Itchhaporia, Michael S. Parmacek, Ada C. Stefanescu Schmidt, George W. Vetrovec, Thad F. Waites, John J. Warner
Journal: Journal of the American College of Cardiology (2022)
DDX41 coordinates RNA splicing and transcriptional elongation to prevent DNA replication stress in hematopoietic cells
Authors: Satoru Shinriki, Mayumi Hirayama, Akiko Nagamachi, Akihiko Yokoyama, Takeshi Kawamura, Akinori Kanai, Hidehiko Kawai, Junichi Iwakiri, Rin Liu, Manabu Maeshiro, Saruul Tungalag, Masayoshi Tasaki, Mitsuharu Ueda, Kazuhito Tomizawa, Naoyuki Kataoka, Takashi Ideue, Yutaka Suzuki, Kiyoshi Asai, Tokio Tani, Toshiya Inaba, Hirotaka Matsui
Journal: Leukemia (2022)

Abstract Myeloid malignancies with DDX41 mutations are often associated with bone marrow failure and cytopenia before overt disease manifestation. However, the mechanisms underlying these specific conditions remain elusive. Here, we demonstrate that loss of DDX41 function impairs efficient RNA splicing, resulting in DNA replication stress with excess R-loop formation. Mechanistically, DDX41 binds to the 5′ splice site (5′SS) of coding RNA and coordinates RNA splicing and transcriptional elongation; loss of DDX41 prevents splicing-coupled transient pausing of RNA polymerase II at 5ʹSS, causing aberrant R-loop formation and transcription-replication collisions. Although the degree of DNA replication stress acquired in S phase is small, cells undergo mitosis with under-replicated DNA being remained, resulting in micronuclei formation and significant DNA damage, thus leading to impaired cell proliferation and genomic instability. These processes may be responsible for disease phenotypes associated with DDX41 mutations.
Comparing dedicated and designated approaches to integrating task-shared psychological interventions into chronic disease care in South Africa: a three-arm, cluster randomised, multicentre, open-label trial
Authors: Bronwyn Myers, Carl J Lombard, Crick Lund, John A Joska, Naomi Levitt, Tracey Naledi, Petal Petersen Williams, Claire van der Westhuizen, Pim Cuijpers, Dan J Stein, Katherine R Sorsdahl
Journal: The Lancet (2022)
Omicron sublineage BA.2.75.2 exhibits extensive escape from neutralising antibodies
Authors: Daniel J Sheward, Changil Kim, Julian Fischbach, Kenta Sato, Sandra Muschiol, Roy A Ehling, Niklas K Björkström, Gunilla B Karlsson Hedestam, Sai T Reddy, Jan Albert, Thomas P Peacock, Ben Murrell
Journal: The Lancet Infectious Diseases (2022)
Lifetime spirometry patterns of obstruction and restriction, and their risk factors and outcomes: a prospective cohort study
Authors: Shyamali C Dharmage, Dinh S Bui, Eugene H Walters, Adrian J Lowe, Bruce Thompson, Gayan Bowatte, Paul Thomas, Judith Garcia-Aymerich, Debbie Jarvis, Garun S Hamilton, David P Johns, Peter Frith, Chamara V Senaratna, Nur S Idrose, Richard R Wood-Baker, John Hopper, Lyle Gurrin, Bircan Erbas, George R Washko, Rosa Faner, Alvar Agusti, Michael J Abramson, Caroline J Lodge, Jennifer L Perret
Journal: The Lancet Respiratory Medicine (2022)
Reconsidering the COVID-19 vaccine strategy in West and Central Africa
Authors: Philippe Msellati, Khoudia Sow, Alice Desclaux, Gilles Cottrell, Mamadou Diallo, Jean-Yves Le Hesran, Geza Harczi, D Abdoulaye Alfa, Abdoulaye Touré, Olivier Manigart
Journal: The Lancet (2022)